Polysaccharides are present as capsules in gram-positive and gram-negative bacteria and as a constituent of the cell wall of bacteria and fungi. Various species of the genera Neisseria, Streptococcus, Klebsiella, Salmonella, Shigella and Haemophilus are pathogenic and are responsible for various human diseases, for example epidemic meningitis, otitis, pneumonia and diarrhoea. These diseases represent a serious global childhood public health problem and therefore, it is important to have a prophylaxis against these diseases.
The polysaccharide macromolecules are comprised of saccharide units which can mediate immunogenicity. Therefore, bacterial polysaccharides or parts thereof have been used for the immunisation of humans. Although, these vaccines are immunogenic in children and adults and can induce protective antibodies, they are not suitable to protect infants because they can only elicit a T-cell independent immune response. Thus, the contact with capsular polysaccharides does not induce a memory response and does not result in a persistent protection. Moreover, it is not possible to elicit an immune response in infants.
To overcome the problem of a T-cell independent immune response, a covalent conjugation of polysaccharides as T-independent antigens to protein carriers as T-dependent antigens has been used and found successful in overcoming this deficiency. Immunisation with such conjugates elicits a T-cell dependent antibody response. However, the choice of carrier proteins which are useful for humans is very restricted, and in most cases, polysaccharides have been coupled to tetanus toxoid, cholera toxoid or diphtheria toxoid. The unlimited or excessive use of these toxoids as carriers is thought to suppress subsequent responses to a polysaccharide coupled to this type of carrier. This suppression of immune response by pre-existing antibodies to the carrier is expected to become a problem in the future.
A further problem which limited the choice of a new carrier protein with regard to this type of conjugate is that the protein has to be non-toxic or detoxified.
Furthermore, known peptide-polysaccharide conjugates suffer from the disadvantage that it is necessary to use an adjuvant to enhance the immune response. However, many known adjuvants are not applicable for humans because they can elicit an inflammatory response. To date, only one adjuvant is permitted for humans: aluminum gel.